Mobility and Quality of Life in Adults with Paediatric-Onset Hypophosphatasia Treated with Asfotase Alfa: Results from UK Managed Access Agreement.

INTRODUCTION: Hypophosphatasia (HPP) is a rare disease caused by deficient tissue-non-specific alkaline phosphatase (ALP) activity. Asfotase alfa is a tissue-non-specific ALP enzyme-replacement therapy which was reimbursed in the UK under a Managed Access Agreement (MAA). This analysis assessed safety and effectiveness of asfotase alfa in adults with HPP. METHODS: This prospective, observational data collection included adults with paediatric-onset HPP enroled in the MAA and treated with asfotase alfa for ≥ 6 months to 5 years. Assessments included mobility, pain, and health-related quality of life (HRQoL), each reported at regular intervals through year 3. Analgesic use, fractures, and events of interest (EOIs) were each reported continuously throughout follow-up. RESULTS: Of 28 enroled treated adults, 24 were assessed for effectiveness. Distance walked in the 6-Minute Walk Test was median (min, max) 172.5 m (0.0, 380.0; n = 24) at baseline and improved by 157.3 m (- 171.0, 479.5; n = 16) at month 6; results were sustained throughout follow-up. Median (min, max) Bleck score was 6.0 (2.0, 9.0; n = 24) at baseline and increased to 6.5 (5.0, 9.0; n = 10) at month 36. Median (min, max) aggregate Brief Pain Inventory Short Form severity score was 8.0 (4.3, 10.0; n = 24) at baseline and improved to 4.4 (1.0, 7.8; n = 10) at month 36. During follow-up, 8 participants (33.3%) decreased or discontinued opioid use throughout follow-up and 4 (16.7%) reported fractures. Median (min, max) EQ-5D-3L utility scores improved from 0.21 (- 0.26, 0.60; n = 24) at baseline by 0.15 (- 0.36, 0.91; n = 24) at month 6 and were similar throughout follow-up. Injection site reactions were the most common treatment-related EOI, reported in 17 participants (60.7%). Three participants reported treatment-related serious adverse events. CONCLUSION: Asfotase alfa treatment improved mobility, physical function, pain, and HRQoL and was well tolerated. These data show the benefit of asfotase alfa in adults with paediatric-onset HPP.